From 8744126d6bf98a042cb9318abb0307246f682b2d Mon Sep 17 00:00:00 2001 From: mwleklin Date: Tue, 2 Mar 2021 16:28:07 -0500 Subject: [PATCH] Add Data back in --- 2_25_2021_Submission.pbtxt | 1879440 +++++++++++++++++++++++++++++++++ 1 file changed, 1879440 insertions(+) create mode 100644 2_25_2021_Submission.pbtxt diff --git a/2_25_2021_Submission.pbtxt b/2_25_2021_Submission.pbtxt new file mode 100644 index 00000000..d93127b7 --- /dev/null +++ b/2_25_2021_Submission.pbtxt @@ -0,0 +1,1879440 @@ +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 4.76 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 4.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 2.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 4.44 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + 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+ identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + 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SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 3.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 86.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 2.11 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 3.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 4.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 2.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 3.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 69.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + 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identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.19 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + 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{ + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + 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+ units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 4.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 2.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 6.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 2.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 3.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.44 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 2.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 3.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 4.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 2.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 3.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 53.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.39 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 2.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 4.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 2.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 6.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 2.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 3.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 78.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 2.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 6.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 2.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 3.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 85.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 2.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 6.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 2.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 4.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 78.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 2.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.76 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 4.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 2.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 4.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 6.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 78.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 2.11 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 69.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 79.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 87.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 6.11 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.11 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 2.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 79.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 80.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 2.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 53.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 3.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 41.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 6.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 2.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 4.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 3.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 4.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 78.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 85.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 85.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 80.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 87.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 3.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 67.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.44 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 64.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 4.81 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 89.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 4.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 6.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 77.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 4.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 3.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 6.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 2.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.19 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 6.81 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 6.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 4.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 63.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 3.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 6.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 4.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 3.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 3.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 79.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 4.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 4.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 6.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 2.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 6.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 4.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 4.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 2.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 6.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 67.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 4.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 32.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: 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{ + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + 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identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: 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{ + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: 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amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in 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+ } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 32.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 32.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 32.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 41.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 79.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 85.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 86.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 41.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 96.38 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.44 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 86.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.11 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 59.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 76.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 84.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.81 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 67.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 77.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 36.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 36.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 78.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 76.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 87.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 63.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 95.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 74.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.39 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 96.76 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 87.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 95.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 96.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 81.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 64.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 67.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: 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"CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.81 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 87.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 86.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 78.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 96.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.44 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 67.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 95.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 74.19 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 96.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 67.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.38 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in 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reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 4.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 74.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: 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+ components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + 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SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + 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products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: 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+ components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 32.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.38 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 6.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 6.81 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 79.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 6.81 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 87.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 87.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 89.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 97.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 67.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 45.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura 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"B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 94.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + 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addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 94.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + 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1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 80.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 41.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 97.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 95.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 81.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 65.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 97.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.39 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 63.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 63.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 81.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 59.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.44 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { 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"CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + 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amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 84.39 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + 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identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: 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provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { 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value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in 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identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + 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1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES 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} + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 84.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: 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} + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + 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} + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES 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volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 80.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: 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{ + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + 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value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + 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value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.38 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: 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} + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES 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445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + 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"CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 65.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.11 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + 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+ volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + 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{ + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.76 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + 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+ provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 80.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 67.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 84.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 81.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 59.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 64.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 77.38 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 3.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.39 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 69.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 65.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.76 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.81 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 85.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 77.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 87.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 77.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 81.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 86.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 85.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.19 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 2.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 69.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 87.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 80.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 45.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 84.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 94.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 76.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 89.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 3.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 81.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 89.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 85.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.44 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 69.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 89.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 85.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 74.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 85.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.11 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 53.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 63.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + 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value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 36.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + 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"CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.38 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 96.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 87.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 69.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 84.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 63.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 98.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 94.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 78.44 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 78.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 78.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 79.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 53.11 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 96.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 76.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.39 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 45.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 2.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 87.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 87.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 41.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.11 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 78.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 4.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 36.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 96.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 81.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 64.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 80.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 84.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 86.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.19 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 97.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 84.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 85.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.39 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 36.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 67.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 97.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 85.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 41.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 80.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 81.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 74.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 97.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 84.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.44 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 76.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 96.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 89.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.38 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 95.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 64.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 87.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 86.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 87.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 65.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 67.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 4.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 65.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.76 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.76 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 84.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 65.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 80.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.76 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 53.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 85.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 65.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 95.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 63.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 86.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.81 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 95.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 95.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 95.19 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 32.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + 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SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + 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+ inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + 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key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 41.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + 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+ inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + 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in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + 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key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + 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2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 80.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + 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wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 94.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 94.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 77.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 87.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 97.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 6.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 89.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: 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} + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 69.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 69.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.44 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 65.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 74.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.11 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 64.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 67.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 64.39 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: 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"Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } 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from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + 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+ type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + 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"Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + 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"HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + 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S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: 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reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + 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{ + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: 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"CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: 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components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + 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units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.19 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + 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value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 41.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: 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amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 45.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 96.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.76 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 63.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 94.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 87.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 77.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 89.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 64.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 81.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 64.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 85.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 77.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 89.81 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 86.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 32.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 94.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 59.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 69.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 94.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 74.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 67.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 67.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 95.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 80.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 64.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 80.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 76.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 64.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 45.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 53.38 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 94.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 87.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 84.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 95.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 87.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 89.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 86.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 76.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 94.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 84.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 86.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 87.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 87.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 84.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 96.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 76.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 87.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 95.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 80.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 79.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 89.19 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 86.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 81.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 85.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 65.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 79.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 89.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 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"CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 81.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 86.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 89.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 85.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 69.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 81.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 98.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 94.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 94.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 85.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 85.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 85.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 79.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 87.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 80.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 81.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 80.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 80.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 67.76 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 63.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 77.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 45.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 95.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 94.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 96.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 86.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 76.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 81.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 64.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 74.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.81 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 45.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 63.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.81 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 59.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 45.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 63.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 65.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 65.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 69.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 59.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 64.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 81.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 77.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 77.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 67.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 84.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 81.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 81.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 87.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 84.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 80.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 87.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 74.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 65.38 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 67.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 67.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 81.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 84.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 69.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 81.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 64.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.38 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 89.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 74.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 87.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 80.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 63.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 89.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 81.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 84.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 65.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.44 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 80.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 87.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 89.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 79.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 76.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 85.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 79.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 80.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 59.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 67.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 85.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 81.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 65.81 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 76.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 96.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 94.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 94.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 86.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 87.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 80.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 79.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 84.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 78.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.38 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 86.11 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 94.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 86.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 86.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 89.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 53.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 89.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 85.76 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.39 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 65.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 67.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 77.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 32.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 96.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 96.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 95.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + 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identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 67.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 94.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + 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} + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 95.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 65.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 94.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 98.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 96.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 77.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 81.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + 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+ identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 89.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 86.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 87.76 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + 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{ + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 89.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in 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+ } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + 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{ + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: 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provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 78.39 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 59.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "B(c1c(ccc2c1cnn2C3CCCCO3)C)(O)O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 78.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 95.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 74.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 67.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 87.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 89.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 80.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: 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details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 69.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 98.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.39 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.76 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 74.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 84.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 36.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 65.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 96.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 84.76 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.19 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 79.44 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 95.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 59.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 95.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 86.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 95.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 80.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 86.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 89.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.39 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 97.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 32.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 65.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 6.38 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 96.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.19 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 95.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 76.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 80.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 85.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + 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{ + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: 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systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + 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moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 53.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 69.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.11 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.44 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 77.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 65.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 64.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 84.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 94.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 79.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 94.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.39 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 96.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 95.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + 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components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 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"HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: 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MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 96.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 94.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 81.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 4.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 67.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 77.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 65.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 89.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 74.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 45.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 89.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 67.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 53.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 77.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 4.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 45.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.44 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 65.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 85.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 45.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 53.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 65.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 79.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 45.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 74.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.39 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 41.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.76 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 36.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 63.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 89.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.38 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 80.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 79.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 41.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 41.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 36.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 36.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 3.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 94.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.38 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 74.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 94.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.39 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.38 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 94.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 86.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 36.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 76.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 76.38 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 65.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 86.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 74.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 4.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.44 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 67.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.76 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + 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+ } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: 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S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + 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+ volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 85.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 84.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 94.39 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 76.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 86.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + 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2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.44 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 78.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 87.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 74.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 76.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 77.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in 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identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: 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provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 77.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 76.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 76.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: 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units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + 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SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + 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doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: 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+ identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: 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provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: 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components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: 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provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD 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+ } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 81.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 76.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 59.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 94.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + 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SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 99.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 86.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 95.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 78.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 81.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 98.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 94.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + 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value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL 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amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 96.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.44 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 65.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 96.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 94.38 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers 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+ amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: 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amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 85.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: 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amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in 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identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: 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provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 84.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 79.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 69.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 79.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 86.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 63.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 36.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 87.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 86.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 81.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 76.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 95.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 94.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in 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volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 63.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 87.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.38 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.19 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 79.38 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 64.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 45.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 41.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + 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"Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 63.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 53.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true 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false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 36.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 79.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 77.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 84.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + 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amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 64.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: 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provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 67.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 65.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 94.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 95.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.19 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 87.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 96.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 95.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 80.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 89.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 96.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 97.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 96.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 84.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 94.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 85.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + 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SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 69.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 80.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 45.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 67.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 89.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 89.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 77.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 65.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 86.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 45.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 74.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + 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amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.81 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + 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Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 94.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 69.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.76 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + 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"Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: 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"CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + 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components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + 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+ provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + 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amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + 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amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 77.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + 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identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 94.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 65.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 80.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 45.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 67.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 85.38 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD 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+ } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 80.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 65.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 94.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 81.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 85.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 59.38 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 95.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 96.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 89.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 96.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 89.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.81 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 76.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 86.44 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 69.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 32.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 95.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 95.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + 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} + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 74.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: 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reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + 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+ units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: 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+ identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + 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components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + 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{ + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 80.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 89.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 84.38 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 84.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 74.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 81.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 80.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 77.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 87.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 86.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 86.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 67.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 81.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 79.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 74.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 67.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 77.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 76.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.19 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 77.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 85.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 78.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 80.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 78.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 86.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 87.81 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 78.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 84.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 85.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 100.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 89.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 100.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 86.19 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 100.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 85.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 85.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 64.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 78.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 84.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 76.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 59.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 78.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 67.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 41.39 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 64.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 63.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 41.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 89.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 87.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 85.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 67.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 59.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 53.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.39 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 36.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 59.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.11 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 53.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 81.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 74.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 78.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 89.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 74.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 85.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 87.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 76.39 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 67.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 77.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 6.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 86.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 81.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 53.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 74.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.11 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 53.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 41.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 78.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 95.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 87.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 79.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.81 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 6.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 94.76 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 84.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 87.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 3.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 67.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 77.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 3.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 3.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 63.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 69.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 76.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 36.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 41.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 84.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 87.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 65.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 45.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 95.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 84.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 89.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 69.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 96.19 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 84.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 3.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 96.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 89.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 94.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 87.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 78.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 4.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 95.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 90.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 89.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.19 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 93.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 74.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.11 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 76.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 79.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 64.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 65.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 6.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 6.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 69.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.81 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.19 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 3.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 36.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 36.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 3.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.38 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.81 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.19 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 3.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 64.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 67.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 64.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 63.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 45.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 78.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.39 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 69.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 64.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 4.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 80.76 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 64.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 6.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.19 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 80.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 45.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.76 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 45.11 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.44 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 64.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.11 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 3.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 59.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in 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{ + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 79.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + 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components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 64.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: 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} + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + 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amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: 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+ } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: 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provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 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+ value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { 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} + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 3.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 64.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.81 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 2.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.19 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.44 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 63.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 65.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 59.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 67.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 69.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 53.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 77.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 63.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 69.81 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 53.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.11 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 3.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 45.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 2.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 4.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 2.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 41.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: 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{ + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 6.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 76.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.44 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 76.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 77.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 69.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.11 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 6.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 74.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 81.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.39 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 76.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.44 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 67.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.44 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 64.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.76 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.44 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 78.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.11 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 4.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + 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reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 67.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + 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+ value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 3.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.76 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.19 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.81 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 3.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 6.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + 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{ + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 53.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + 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false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + 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components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + 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"Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + 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"Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 79.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 4.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 77.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 3.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.11 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 76.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.76 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 6.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 77.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 69.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 84.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.38 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 86.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.19 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 32.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 6.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 4.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.76 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.19 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 6.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.19 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.39 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.81 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 6.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.19 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 63.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.38 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.39 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.38 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 3.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.44 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.81 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 6.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 6.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 65.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 6.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.44 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.76 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 6.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccc2n(C3CCCCO3)ncc2c1B4OC(C)(C)C(C)(C)O4" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.76 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.38 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.76 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.11 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.19 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 69.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 32.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + 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reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 41.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 53.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + 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+ key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + 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units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 32.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + 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components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.39 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + 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components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 84.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.39 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 32.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 32.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 74.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + 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moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + 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"CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + 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"Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.38 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.44 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 32.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.19 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + 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components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 36.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 32.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.11 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.76 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 36.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 45.38 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.38 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 74.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 32.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 59.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 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reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 36.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 63.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: 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"CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 53.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 69.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 41.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 45.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 84.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 64.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "O=S(OC1=CC=C2N=CC=CC2=C1)(C(F)(F)F)=O" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: 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+ } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + 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value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + 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key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: 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and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 36.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + 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reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.38 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 4.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.39 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + 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SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + 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amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: 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amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in 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identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } 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false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.44 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + 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identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: 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amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: 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identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: 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provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: 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provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.44 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.19 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + 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+ identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: 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provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { 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of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.76 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.11 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.11 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.44 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 36.44 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 32.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 41.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 32.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.11 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.81 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.44 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.39 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 41.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 53.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 32.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 41.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.76 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.39 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.38 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in 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amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + 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"Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + 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"Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.81 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.39 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + 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components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + 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components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.44 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 45.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 63.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 53.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 69.39 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 69.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 64.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 63.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 78.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 63.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 69.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 64.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 76.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.38 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 65.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 53.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 81.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 69.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 80.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 76.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 80.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 74.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 79.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 81.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 53.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 82.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 78.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 84.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 74.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 59.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 59.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 78.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 78.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 76.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 67.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "IC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.81 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.81 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 53.11 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.38 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: 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} + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + 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+ amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: 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amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: 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amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: 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identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: 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provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: 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} + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + 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+ amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: 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amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: 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amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: 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identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: 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provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.76 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: 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type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + 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details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: 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"C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: 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components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + 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+ provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: 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reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: 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"C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + 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components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + 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+ provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: 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addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + 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inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + 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volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + 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+ identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.38 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: 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"C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + 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identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: 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provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: 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1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.81 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: 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identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: 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provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in 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+ reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.81 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: 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type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + 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addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: 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provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: 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+ value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + 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identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED 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detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED 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detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.76 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.44 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + 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SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: 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provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: 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+ value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 74.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 41.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + 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+ type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: 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amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 74.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" 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identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: 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+ identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + 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{ + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 41.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 6.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 63.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 59.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.39 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 59.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 59.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + 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"O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: 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CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + 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+ type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 74.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.44 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 64.11 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 65.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.11 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 64.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + 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identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 74.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 32.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 45.81 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.19 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + 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identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 59.44 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 41.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { 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} + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + 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components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.19 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.19 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.44 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.39 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.81 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.76 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.39 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.38 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.11 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.81 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.38 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + 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"CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 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+ type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.19 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + 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MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: 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components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.44 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: 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components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: 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components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + 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"CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + 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"CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.39 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + 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} + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } 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SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + 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+ identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: 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SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + 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+ identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + 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SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + 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key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } 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value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED 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detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + 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+ addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.38 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 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+ type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + 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445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: 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value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + 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components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + 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value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + 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components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + 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+ identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: 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SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: 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+ value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.19 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } 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1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.81 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.39 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + 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"O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: 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+ type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + 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+ } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: 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CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 41.19 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: 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+ identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.76 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 41.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 59.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + 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+ outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + 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"O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: 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+ type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + 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+ } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + 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reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + 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+ components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.44 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.39 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.38 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "ClC1=CC=C2N=CC=CC2=C1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "F[B-](F)(C1=C(C)C=CC2=C1C=NN2C3CCCCO3)F.[K+]" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 45.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 63.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 45.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 80.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 79.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 65.44 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 78.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 65.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + 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+ } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 69.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 83.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 92.19 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 41.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 36.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: 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value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in 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identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR 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"San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + 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value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + 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provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 65.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 59.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 69.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 59.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.81 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 45.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.11 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.39 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.76 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 41.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + 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identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 41.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 41.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + 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identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 65.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 36.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 32.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 36.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 36.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.81 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + 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"C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + 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} + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 32.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + 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reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: 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reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 65.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 36.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 45.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 64.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + 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"OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 45.11 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 59.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "OB(C1=CC=C2N=CC=CC2=C1)O.[H]Cl" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 32.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 36.19 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 36.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 59.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 41.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 59.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 67.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 59.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 64.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 32.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 32.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 45.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 64.81 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in 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{ + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in 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+ identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 32.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.76 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 36.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 32.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 41.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 64.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 64.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 41.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 45.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 59.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 36.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 53.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 59.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 59.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 59.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 59.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 63.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 64.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 81.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 32.76 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 59.81 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 69.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 36.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 63.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 53.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 32.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.62 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 41.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.81 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 59.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 53.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 32.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 36.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 45.11 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 41.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 41.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 36.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 32.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 91.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST 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type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 41.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST 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type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.68 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 53.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 53.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[K+].F[B-](F)(F)c1ccc2ncccc2c1" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "[H]O[H]" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 73.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 53.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.19 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 53.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.31 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 45.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 59.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 77.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 41.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 66.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.7 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.81 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 77.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + 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reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + 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+ } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + 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is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate 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{ + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.24 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + 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} + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in 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is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in 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+ value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.19 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.54 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 21.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 76.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.19 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 80.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 41.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CO" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 18.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 23.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 53.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 79.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 65.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 77.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 69.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.81 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.28 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 59.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 88.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 75.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 81.94 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.38 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 64.23 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.11 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 45.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 59.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.99 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.96 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.37 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 65.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 36.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.95 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 80.57 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 81.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.07 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 67.88 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 74.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 67.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 36.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CC#N" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.41 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.81 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.25 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 67.5 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 64.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 63.08 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + 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"CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 77.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 63.19 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 36.75 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 53.83 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.1 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.93 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + 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"CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.76 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.87 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 43.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.61 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 77.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 79.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 53.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.56 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 80.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 70.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 65.05 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 64.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 71.14 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.66 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 72.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 68.72 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.6 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.02 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 53.77 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 59.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.91 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.76 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.34 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 60.06 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + 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+ value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 36.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + 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SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 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SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: 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identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.46 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 61.3 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.17 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } 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+ } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { 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amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + 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+ } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + 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+ } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.59 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 45.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 58.39 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.51 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.92 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 42.35 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 52.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 37.85 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.01 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: 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+ } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + 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identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + 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components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + 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value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.27 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.76 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 62.19 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.13 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.22 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.33 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.9 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.97 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.09 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 45.45 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.42 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 24.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.43 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 27.48 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 45.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[OH-].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.12 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 33.69 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 57.78 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + 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is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 30.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + 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"Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 36.03 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.58 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[Li+].CC(C)(C)[O-]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "CCCCCC" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 9.18 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 77.29 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.53 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 50.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.65 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.8 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.16 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C(=O)(O)[O-].[Na+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.15 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.86 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.4 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 46.73 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 49.52 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 53.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 38.04 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.79 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 44.82 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.26 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCN(CC)CC" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "C1CCOC1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.64 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 59.89 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.49 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 45.67 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.55 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.63 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.36 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 48.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.32 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[F-].[Cs+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C(C)(C)C)C(C)(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P(c2ccccc2)c3ccccc3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 77.47 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.CC(C)(C)P(C1=CC=C(C=C1)N(C)C)C(C)(C)C.Cl[Pd]Cl" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 55.98 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3CCCCC3" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 51.74 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1P(c2ccccc2C)c3ccccc3C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + 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+ } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { 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amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CCCCP([C@@]12C[C@H]3C[C@@H](C1)C[C@@H](C2)C3)[C@@]45C[C@H]6C[C@@H](C4)C[C@@H](C5)C6" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 56.84 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "COc1cccc(c1c2ccccc2P(C3CCCCC3)C4CCCCC4)OC" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 69.71 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.CC(C)(C)P([C]1[CH][CH][CH][CH]1)C(C)(C)C.[Fe]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 47.21 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(C)c1cc(c(c(c1)C(C)C)c2ccccc2P(C3CCCCC3)C4CCCCC4)C(C)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "c1ccc(cc1)P([c-]2cccc2)c3ccccc3.c1ccc(cc1)P([c-]2cccc2)c3ccccc3.[Fe+2]" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.44 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(c2cccc(c2Oc3c1cccc3P(c4ccccc4)c5ccccc5)P(c6ccccc6)c7ccccc7)C" + } + amount { + moles { + value: 0.05 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 0.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +} +reactions { + identifiers { + type: NAME + value: "Suzuki-Miyaura cross-coupling" + } + inputs { + key: "Aryl Halide" + value { + components { + identifiers { + type: SMILES + value: "BrC1=C(C)C=CC2=C1C=NN2C3CCCCO3" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "CCC1=CC(CC)=CC=C1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Base in Solvent" + value { + components { + identifiers { + type: SMILES + value: "[O-]P(=O)([O-])[O-].[K+].[K+].[K+]" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Boronate in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC1(OB(C2=CC=C3N=CC=CC3=C2)OC1(C)C)C" + } + amount { + moles { + value: 0.4 + units: MICROMOLE + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: SMILES + value: "O=CN(C)C" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "CC(C)(C)c1ccc(cc1)c2ccc(cc2)C(C)(C)C" + } + amount { + moles { + value: 0.4 + precision: 0.4 + units: MICROMOLE + } + } + reaction_role: INTERNAL_STANDARD + } + addition_order: 1 + } + } + inputs { + key: "Catalyst in Solvent" + value { + components { + identifiers { + type: SMILES + value: "CC(=O)[O-].CC(=O)[O-].[Pd+2]" + } + amount { + moles { + value: 0.025 + units: MICROMOLE + } + } + reaction_role: CATALYST + } + components { + identifiers { + type: SMILES + value: "CCc1cc(CC)cc(CC)c1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Ligand in Solvent" + value { + components { + identifiers { + type: SMILES + value: "Cc1ccccc1" + } + amount { + volume { + value: 1.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + } + } + inputs { + key: "Solvent_1" + value { + components { + identifiers { + type: SMILES + value: "CN(C)C=O" + } + amount { + volume { + value: 445.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + components { + identifiers { + type: SMILES + value: "O" + } + amount { + volume { + value: 49.5 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + } + addition_order: 1 + addition_speed { + type: FAST + } + flow_rate { + value: 1.0 + units: MILLILITER_PER_MINUTE + } + addition_device { + type: SYRINGE + details: "HPLC Pump" + } + } + } + setup { + vessel { + type { + type: TUBE + } + material { + type: CUSTOM + details: "Hastelloy" + } + volume { + value: 710.0 + units: MICROLITER + } + } + is_automated: true + environment { + type: GLOVE_BOX + } + } + conditions { + temperature { + setpoint { + value: 100.0 + units: CELSIUS + } + } + pressure { + control { + type: PRESSURIZED + } + setpoint { + value: 100.0 + units: BAR + } + } + flow { + flow_type { + type: PLUG_FLOW_REACTOR + } + tubing { + type: STEEL + details: "Hastelloy" + diameter { + value: 0.5 + units: MILLIMETER + } + } + } + conditions_are_dynamic: false + } + outcomes { + reaction_time { + value: 1.0 + units: MINUTE + } + products { + identifiers { + type: SMILES + value: "CC(C=C1)=C(C2=CC=C(N=CC=C3)C3=C2)C4=C1N(C5OCCCC5)N=C4" + } + is_desired_product: true + measurements { + analysis_key: "Agilent 1200 Infinity HPLC systems" + type: YIELD + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 54.2 + } + } + reaction_role: PRODUCT + } + analyses { + key: "Agilent 1200 Infinity HPLC systems" + value { + type: LCMS + details: "HPLC S4\nconditions uses a 0.1% AcOH/NH4COOH/Water based gradient over 1.4 minutes running from 5-95% MeCN using a Waters Acquity UPLC BEH C18 30 x 2.1 mm column at 80 \302\260C with a flow rate of 2.5ml/min and a detection wavelength of 210 360nm" + instrument_manufacturer: "Agilent" + } + } + } + provenance { + city: "San Diego, CA" + doi: "10.1126/science.aap9112" + publication_url: "https://science.sciencemag.org/content/359/6374/429" + record_created { + time { + value: "2/25/2021, 1:05:42 PM" + } + person { + name: "Michael Wleklinski" + orcid: "0000-0001-6735-4696" + organization: "Merck" + email: "michael.wleklinski@merck.com" + } + } + } +}